Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals
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Date
2011
Journal Title
Journal ISSN
Volume Title
Publisher
Malaria Research and Treatment
Abstract
Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART) poses significant challenges. Artemetherlumefantrine
(AL) is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug
combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine
aremetabolized by hepatic cytochrome P450 (CYP450) enzymes which metabolize the protease inhibitors (PIs) and nonnucleoside
reverse transcriptase inhibitors (NNRTIs) used forHIV treatment. Coadministration of NNRTIs and PIs with AL could potentially
cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4
enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and
desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There
are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target
populations are urgently needed.
Description
Keywords
Artemether-Lumefantrine Combination Therapy, Treatment of Uncomplicated Malaria, Antiretroviral Drugs, HIV-Infected Individuals
Citation
Byakika-Kibwika, P., Lamorde, M., Mayanja-Kizza, H., Khoo, S., & Merry, C. (2011). Artemether-lumefantrine combination therapy for treatment of uncomplicated malaria: the potential for complex interactions with antiretroviral drugs in HIV-infected individuals. Malaria research and treatment , doi:10.4061/2011/703730